Effect of pH Change on Vascular Smooth Muscle Contractility in Rat Superior Mesenteric Artery and Its Branches

Choi, Soo Seung

Abstract

BACKGROUND
Extracellular and intracellular pH (pHo and pHi), which can be changed in various pathological conditions such as hypoxia, affects vascular contractility. To elucidate the mechanism to alter vascular contractility by pH, the effects of pH on reactivity to vasocontracting agents, intracellular Ca2+ influx, and Ca2+ sensitivity in vascular smooth muscle were examined. MATERIAL AND METHOD: Isometric contractions in rat superior mesenteric arteries (SMA) were observed. Intracellular Ca2+ concentration ([Ca2+]i) was recorded by microfluorometer using Fura-2/acetoxylmethyl ester in muscle cells. pHo was increased from 7.4 to 7.8 or decreased to 6.9 or 6.4. pHi was decreased by applying NH4+ or propionic acid or modulated by changing pHo after increasing membrane permeability using beta-escin. RESULT: Decreases in pHo from 7.4 to 6.9 or 6.4 shifted concentration-response curve by norepinephrine (NE) or serotonin (SE) to the right and significantly increased half maximal effective concentration (EC50) to NE or SE. Increase in pHo from 7.4 to 7.8 shifted concentration-response curve by norepinephrine (NE) or serotonin (SE) to the left and significantly reduced EC50 to NE or SE. NE increased [Ca2+]i in cultured smooth muscle cells from SMA and the increased [Ca2+]i was reduced by decreases in pHo. NE-induced contraction was inhibited by NH4+, whereas the resting tension was increased by NH4+ or propionic acid. When the cell membrane of SMA was permeabilized using beta-escin, SMA was contracted by increasing extracellular Ca2+ concentration from 0 to 10micrometer and the magnitude of contraction was decreased by a decrease in pHo and vice versa.
CONCLUSION
From these results, it can be concluded that a decrease in pHo might inhibit vascular contraction by reducing the reactivity of vascular smooth muscle to vasoactive agents, Ca2+ influx and the sensitivity of vascular smooth muscle to Ca2+.